Microfragmented Adipose Tissue: New Evidence for Osteoarthritis Treatment
August 5, 2025
Microfragmented adipose tissue represents a promising biological treatment for patients suffering from osteoarthritis who have not responded to conventional therapies. Osteoarthritis affects over 32.5 million adults in the United States alone, with current treatments often providing only temporary relief or carrying significant side effects.
Unlike traditional interventions, microfragmented adipose tissue (MFAT) harnesses the regenerative properties of mesenchymal stem cells naturally present in fat tissue. These cells can potentially reduce inflammation, promote tissue repair, and consequently improve function in damaged joints. Furthermore, recent clinical trials have shown that MFAT injections can significantly decrease joint pain for up to 12 months following a single treatment. Though not yet FDA approved for widespread use in osteoarthritis, the mounting evidence supporting MFAT’s efficacy has sparked considerable interest in the orthopedic community. With that being said, there are several FDA aproved devices for the MFAT harnessing.
This article examines the latest research on microfragmented adipose tissue for osteoarthritis treatment, including patient selection criteria, harvesting techniques, clinical outcomes, and comparative efficacy against other injectables. Additionally, we’ll explore the cellular composition that makes this therapy uniquely effective for joint preservation and pain management.
Patient Selection Criteria for MFAT Trials
Careful patient selection remains essential for optimizing outcomes in microfragmented adipose tissue (MFAT) treatments for osteoarthritis. Clinical trials have established specific inclusion and exclusion criteria to identify suitable candidates while ensuring study validity and patient safety.
Kellgren-Lawrence Grades 1-4 Inclusion
The radiographic severity of knee osteoarthritis typically determines eligibility for MFAT trials, with most studies accepting patients across the spectrum of Kellgren-Lawrence (KL) classifications. Specifically, numerous trials include patients with KL grades 1-4, acknowledging various stages of disease progression [1]. However, the distribution of enrolled patients often skews toward moderate disease severity. In one notable study, researchers reported a distribution of 31.3% grade 1, 61.2% grade 2, and 7.5% grade 3 patients [2].
Interestingly, patient responses to MFAT treatment appear to correlate with disease severity. Data indicates response rates of 100% for grade 1 (5/5 patients), 73.9% for grade 2 (17/23 patients), 47.2% for grade 3 (26/55 patients), and 55.6% for grade 4 (10/18 patients) [3]. This suggests that while MFAT remains suitable across all grades, earlier intervention may yield superior outcomes.
Some trials narrow their focus to specific KL grade ranges—either grades 2-3 [1] or grades 3-4 [4]—depending on research objectives and treatment protocols. Regardless of grade inclusion, all participants must demonstrate symptomatic knee pain despite prior conservative treatment attempts, establishing MFAT as a secondary intervention option.
Exclusion of Patellofemoral OA and Severe Effusion
Several anatomical and pathological factors commonly disqualify patients from MFAT studies. Notably, isolated patellofemoral osteoarthritis represents a standard exclusion criterion [1]. Similarly, patients presenting with grade 3 or higher knee effusion (based on the stroke test grading system) are typically excluded [1], as excessive fluid accumulation may compromise treatment delivery and efficacy.
Structural considerations also influence patient selection. Most trials exclude candidates with:
- Valgus or varus deformities exceeding 10 degrees [1]
- Recent knee injury (within 3 months) [5]
- Previous intra-articular steroid injections (within 3 months) [5]
- Lower limb malalignment greater than 8-10 degrees [6]
- Evidence of concurrent anterior cruciate ligament tear [6]
Moreover, systemic factors necessitating exclusion include infectious joint disease, malignancy, pregnancy, coagulation disorders, and alcohol or substance abuse history [7]. These precautions minimize confounding variables while prioritizing patient safety during experimental treatments.
BMI and Age Range Requirements
Body mass index (BMI) and age specifications feature prominently in MFAT trial criteria, primarily to control for metabolic variables and regenerative capacity. Most studies establish an upper BMI limit of 40 kg/m² [1], although some implement stricter thresholds of 35 kg/m² [4] or 30 kg/m² [4]. These limitations acknowledge the potential impact of obesity on treatment outcomes and procedural safety.
Age eligibility typically spans 25-75 years [1], balancing the need for biological responsiveness with the prevalence of osteoarthritis in older populations. Nonetheless, actual enrollment demographics often skew toward older patients, with one study reporting a mean participant age of 71.1 years (range 47.0-94.9) [8] and another documenting ages from 42 to 94 years [7].
The mean BMI across trial participants generally falls within the overweight category—approximately 28.4 kg/m² (range 19-37) in one representative study [8]. This reflects the real-world association between elevated BMI and osteoarthritis development while remaining within treatment feasibility parameters.
Ultimately, these stringent selection criteria serve to identify patients most likely to benefit from MFAT therapy while minimizing confounding factors that could obscure treatment efficacy assessment.
MFAT Harvesting and Injection Protocols
The standardized protocol for obtaining and administering microfragmented adipose tissue involves three critical phases: harvesting adipose tissue via lipoaspiration, processing the lipoaspirate using mechanical systems, and precisely delivering the final product through ultrasound-guided injection.
Lipoaspiration Technique Using Klein Solution
The harvesting procedure typically targets subcutaneous fat from the lower or lateral abdomen, though alternative sites may be used for patients with limited abdominal adipose tissue. Initially, a small incision (subcentrimetric) is made at the donor site to facilitate access [8]. Prior to extraction, tumescent anesthesia using Klein solution is administered to minimize patient discomfort and reduce bleeding during harvesting. The standard composition includes saline solution (250 mL), lidocaine 2% (25-40 mL), and epinephrine at a dilution of 1:1,000 (0.5-1 mL) [1].
A 17-gage blunt cannula connected to a 60-mL Luer-lock syringe delivers the anesthetic solution into the subcutaneous tissue [1][8]. After allowing approximately 5-10 minutes for the solution to take effect, the adipose tissue is harvested using a 13-gage blunt cannula connected to a 20-mL vacuum-locked syringe [1][8][8]. The extraction technique involves a gentle “violin movement” across both superficial and deep fat layers [1]. This manual approach yields superior stem cell viability compared to device-assisted methods [3].
Mechanical Processing with Lipogems System
Once collected, the lipoaspirate undergoes mechanical processing using the Lipogems system (Lipogems International SpA, Milan, Italy), a closed-loop, disposable device designed for single surgical sessions [9]. This FDA-approved system mechanically fragments adipose tissue while preserving its structural integrity and cellular components [10].
The processing sequence follows several steps:
- Transfer of harvested lipoaspirate into the cylindrical Lipogems device containing stainless steel balls [1]
- Initial size reduction by pushing the tissue through a first filter while saline exits toward a waste bag [1]
- Mechanical agitation that fragments oily residues and eliminates blood components through gravity [1]
- Continuous saline washing until the solution becomes transparent and adipose tissue appears light yellow [1]
- Secondary size reduction by passing the floating adipose clusters through a narrower filter [1]
- Decanting of excess saline and transfer of the final MFAT product into 10-mL syringes [1]
The entire processing cycle takes approximately 15-20 minutes and requires no enzymatic digestion or centrifugation [11]. This gentle mechanical approach preserves the stromal vascular niche and cellular microarchitecture while yielding a fluid, uniform product suitable for injection through small-gage needles [11][10].
Ultrasound-Guided Intra-articular Injection
For optimal placement accuracy, ultrasound guidance has emerged as the gold standard for MFAT intra-articular injections [4]. Compared to blind injections, ultrasound guidance significantly improves needle placement accuracy (96% vs. 77%) [7].
The most common approach for knee osteoarthritis is the lateral suprapatellar technique [8]. With the patient positioned supine and the knee fully extended, a high-frequency linear transducer visualizes the target area [4][7]. After standard skin disinfection with povidone-iodine or chlorhexidine, an 18-gage needle delivers approximately 4-8 mL of the processed MFAT directly into the joint space [12][13].
For patients lacking visible effusion, alternative approaches include inferolateral or inferomedial techniques targeting the femoral condyle trochlear cartilage [4]. These methods employ in-plane needle advancement with continuous hydrodissection to displace anatomical structures and confirm intra-articular placement [4].
Post-injection protocols typically include using crutches for three days, applying an elastic waistband at the harvesting site for two weeks, and implementing appropriate antithrombotic prophylaxis [12]. These measures ensure optimal recovery at both the donor and recipient sites.
Outcome Measures and Follow-up Timeline
Clinical assessment of microfragmented adipose tissue efficacy requires standardized outcome measures tracked across predetermined intervals. Researchers evaluate both subjective patient-reported improvements and objective functional metrics to establish treatment benefits and duration.
KOOS Subscales: Pain, ADL, QOL, Sports
The Knee Injury and Osteoarthritis Outcome Score (KOOS) serves as the primary assessment tool in MFAT studies, consisting of five separately scored subscales: Pain (9 items), Symptoms (7 items), Function in daily living (ADL) (17 items), Function in Sport and Recreation (5 items), and knee-related Quality of Life (QOL) (4 items) [14]. Each subscale transforms raw scores to a 0-100 scale, with 100 representing no knee problems and 0 indicating extreme difficulties [14]. This self-administered instrument requires approximately 10 minutes to complete [14].
MFAT interventions consistently demonstrate substantial improvements across all KOOS domains. In representative studies, baseline KOOS pain scores averaging 51.1 rise to 77.8 at 12-month follow-up [5]. Similarly, ADL function scores typically improve from baseline values of 61.1 to 83.7 at one year post-treatment [5]. The Sport/Recreation subscale often shows the most dramatic improvement, with studies reporting increases from 27.9 at baseline to 57.7 at 12 months [5]. Likewise, QOL scores frequently double from initial assessments (30.1) to final follow-up (61.1) [5].
VAS Pain Score Tracking at 1, 3, 6, 12 Months
The Visual Analog Scale (VAS) provides a complementary pain assessment, tracking subjective discomfort on a 0-100 scale. Patients typically undergo evaluation at 1, 3, 6, and 12 months post-injection to establish both immediate and sustained effects. Multiple studies report significant VAS improvements from baseline (49.8) to 3 months (15.4) that maintain through 12-month follow-up (23.4) [5].
Long-term data indicate lasting benefits extending beyond one year. According to comprehensive three-year studies, VAS pain scores decrease from pre-operative values of 43.49 to 25.86 at 3 months, with sustained improvement (28.99) at 36 months [15]. Statistical analyzes confirm these reductions remain significant throughout follow-up periods (p<0.001) [15].
Tegner Activity Level Assessment
The Tegner activity scale quantifies functional improvement by measuring patients’ ability to return to specific activities. This validated instrument assesses activity levels on a 0-10 scale, with higher scores indicating greater functional capacity. Following MFAT treatment, studies report meaningful increases from baseline values of 3.0 to 4.2 at 12 months [5].
Comparative analyzes between MFAT and platelet-rich plasma (PRP) injections reveal interesting patterns in Tegner scores. At 6 months post-treatment, MFAT patients demonstrate statistically superior Tegner improvements compared to PRP recipients (p=0.02) [2]. Nevertheless, both interventions yield clinically significant functional gains compared to saline controls [6].
Crucially, early outcome improvements strongly predict long-term benefits. Statistical analyzes reveal that clinical improvements at 3 months post-operation reliably forecast sustained benefits at 1, 2, and 3 years (p<0.05) [15], hence enabling early identification of likely treatment responders.
Comparative Efficacy with PRP and Saline
Recent randomized controlled trials have directly compared microfragmented adipose tissue with established injectable treatments to objectively evaluate relative efficacy for osteoarthritis management.
12-Month KOOS-Pain Score Comparison with PRP
In head-to-head comparisons between microfragmented adipose tissue (MFAT) and platelet-rich plasma (PRP), both treatments demonstrated substantial clinical improvements with remarkably similar outcomes. At 12 months post-treatment, KOOS-Pain scores showed virtually identical results between PRP (78 ± 17.9) and MFAT (77.8 ± 19.3) with no statistically significant difference (p = .69) [3]. This pattern of equivalence extended across all KOOS subscales, including symptoms, activities of daily living, sports/recreation, and quality of life [16]. Interestingly, even at earlier follow-up points (6 months), both interventions showed comparable improvement from baseline in KOOS-Pain measures, with MFAT improving from 58.4 ± 15.9 to 75.8 ± 17.4 and PRP from 63.5 ± 17.8 to 75.5 ± 16.1 [17].
Difference-in-Difference Analysis vs Saline
Beyond simple before-after comparisons, difference-in-difference evaluations provide more sophisticated analysis of treatment effects versus controls. Through this methodology, researchers found MFAT injection resulted in KOOS-Pain scores improving by 27.8 points at 12 months compared to saline [18]. Similarly, quality of life scores improved by 28.1 points above saline controls [18]. Visual Analog Scale (VAS) pain measurements further support MFAT efficacy, with mean pre-operative VAS scores of 44 decreasing to 28 at 6-months post-injection [19].
MCID Threshold Achievement in All Groups
The clinical relevance of statistical improvements ultimately depends on reaching Minimal Clinically Important Difference (MCID) thresholds—the smallest change patients perceive as beneficial. For KOOS-Pain, both MFAT and PRP groups surpassed MCID thresholds by 1 month post-treatment and maintained this improvement throughout the 12-month study period [3]. Overall response rates in the MFAT group reached 63% of patients, with 64% of responders qualifying as “super-responders” by showing VAS pain score reductions of 20 points or more [19]. For functional outcomes measured by Oxford Hip Score, 81% of MFAT recipients responded positively, with 50% achieving super-responder status [19].
Interestingly, patient satisfaction metrics like Patient Acceptable Symptom State (PASS) showed high achievement rates at both 6 months (87%) and 12 months (86%) post-treatment [20]. This correlates with MCID achievement percentages of 89.8% at 6 months and 85.6% at 12 months [20], effectively demonstrating that most patients experience clinically meaningful improvements from MFAT therapy.
Cellular Composition and Statistical Analysis
The biological foundation of microfragmented adipose tissue therapy relies on its unique cellular composition and rigorous analytical validation methods.
Stromal Vascular Fraction (SVF) Viability in MFAT
Processed MFAT samples contain a heterogeneous stromal vascular fraction (SVF) with documented therapeutic properties. SVF isolation involves washing samples with phosphate-buffered saline, collagenase digestion, neutralization with DMEM containing 10% fetal bovine serum, and centrifugation at 800g for 5 minutes [3]. This process separates the SVF pellet from adipocytes while preserving cellular viability. Studies consistently report SVF viability rates between 78% and 91% as determined via Trypan blue dye exclusion [21]. SVF cellular components include adipose-derived stem cells (expressing CD105+, CD73+, CD90+, CD44+), CD146+ pericytes, CD31+ endothelial cells, and CD34+ hematopoietic cells [8].
Total Nucleated Cell Count via Hemocytometer
Total nucleated cell count (TNC) quantification employs standardized hemocytometer methodology. In this technique, cell suspensions are filtered through 40-μm cell strainers [3], then diluted appropriately (typically 1:10) with HBSS or PBS [13]. The counting chamber, designed to hold precisely 0.1mm³ of solution, features gridded squares that facilitate systematic counting [22]. Cell concentration calculations follow the formula: Total cells/mL = average cell count per square × dilution factor × 10⁴ [23]. This standardized approach ensures consistent cell quantification across studies.
Power Analysis and Repeated Measures ANOVA
Statistical validation of MFAT studies relies on predetermined power calculations. Most trials target 80% statistical power with significance levels of 0.01-0.05 [8]. Sample size determinations consider minimal clinically important difference (MCID) thresholds—typically 9 points for KOOS-Pain subscales [3]. Data analysis primarily employs repeated-measures ANOVA with post-hoc testing to evaluate treatment effects across multiple timepoints [3]. Continuous variables undergo distribution testing via Shapiro-Wilk test [8], with non-parametric alternatives (Mann-Whitney U test) applied when appropriate [21].
Conclusion
Microfragmented adipose tissue therapy represents a significant advancement in osteoarthritis treatment based on mounting clinical evidence. The comprehensive patient selection criteria, standardized harvesting techniques, and precise injection protocols collectively ensure optimal outcomes across diverse patient populations. Most importantly, MFAT demonstrates remarkable efficacy in improving both pain and function, with KOOS and VAS measurements showing sustained benefits lasting up to 12 months after a single treatment.
Comparative analyzes reveal that MFAT performs equally well as platelet-rich plasma therapy, while significantly outperforming saline injections. This equivalence to established treatments, coupled with superior results to placebo, strengthens the case for MFAT as a viable therapeutic option. The high percentage of patients achieving minimal clinically important difference thresholds further validates the real-world impact of this intervention.
The biological mechanism underpinning MFAT effectiveness stems from its rich stromal vascular fraction, which maintains excellent cellular viability through careful processing. These regenerative components appear capable of modulating inflammation while promoting tissue repair within damaged joints. Statistical validation through rigorous methodologies confirms these benefits extend beyond random chance or placebo effect.
MFAT therapy fills a critical treatment gap for patients who have exhausted conservative management options yet wish to avoid or delay surgical intervention. Though not yet FDA-approved specifically for osteoarthritis, the accumulating evidence supports its consideration as part of a comprehensive treatment algorithm. Future research should focus on optimizing patient selection parameters, determining ideal dosing schedules, and investigating combination approaches with existing therapies. Undoubtedly, microfragmented adipose tissue has emerged as a promising biological treatment deserving further clinical implementation and investigation in the ongoing battle against osteoarthritis.
References
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